Cardiovascular disease remains the leading cause of morbidity and mortality in industrialized nations. An increase in arterial wall stiffness and thickness is the common pathological pathway for the factors that lead to initiation and progression of the vascular changes associated with cardiovascular disease. Functional disturbances of the vascular wall may occur early in the artherosclerotic process, even before the anatomical changes of intima-media thickening become perceptible. Therefore, study of dynamic and anatomic arterial wall properties of large arteries, such as the carotid and femoral arteries has become commonplace. Since the mechanical and structural properties of the arterial wall may change before the occurrence of clinical symptoms of cardiovascular disease, the non-invasive measurements of arterial wall properties has become common in the study of atherosclerosis and as an extremely important method for identifying individuals at risk for cardiovascular events. Therefore, standardized, improved and easily deployed methods for evaluating arterial wall structures and characteristics has important implications leading to earlier and more effective strategies for screening, prevention and treatment of atherosclerosis and cardiovascular disease.
Direct measurement of the arterosclerotic burden and its rate of progression can be determined by quantitative imaging of vascular structures. The only standardized imaging methodology currently available to determine coronary and cerebrovascular atherosclerosis is angiography. However, this imaging technique is limited to luminal dimensions and only inferences about the extent of arterial wall involvement can be made. Further, since angiographic procedures are invasive, they cannot be performed in asymptomatic persons. Additionally, angiographic measurement of atherosclerosis is a relatively high variability procedure. As such, coronary angiography has no applicability in the screening for and in the prevention of atherosclerosis and cardiovascular disease. Other than B-mode ultrasonography, there is no reliable non-invasive technique available to directly measure atherosclerosis or its progression.
Accordingly, high resolution B-mode ultrasonography can be used to non-invasively and quantitatively image the atherosclerotic process in peripheral vessels reflective of coronary artery and cerebrovascular atherosclerosis. Measurement of carotid arterial wall stiffness and intima-media thickness (IMT) have been shown to reflect early subclinical atherosclerosis. Large epidemiologic and case-control studies have demonstrated an association between carotid arterial wall stiffness and IMT, measured by B-mode carotid ultrasonograpy, and cardiovascular, cerebrovascular and atherosclerosis risk factors in both men and women. The association between coronary and carotid atherosclerosis depends in part on exposure of both arterial beds to the same risk factors. Studies have demonstrated a strong relationship between carotid arterial wall stiffness and IMT and angiographic presence, extent, and progression of coronary artery disease in both men and women. Arterial wall thickness demonstrates as good or better correlation with coronary artery disease than does traditional lipid and non-lipid risk factors. Most importantly, carotid arterial wall stiffness and thickness predict clinical cardiovascular and cerebrovascular events in men and women.
Since the lumen-intima and media-adventitia echoes in carotid ultrasound images were first identified and histologically verified as an accurate measure of intima-media thickness of the arterial wall, B-mode ultrasonography has been used for non-invasive quantitative measurement of intima-media thickness (IMT) as a direct measurement of atherosclerosis. The methodology used to measure IMT has relied on human visual judgment in order to manually identify echo coordinates indicating the lumen-intima and media-adventitia boundaries. The accuracy, reproducibility and precision of IMT measurements, determined by manual identification methods, are limited by human variability in the operation of coordinate designation devices and by the resolution of the displayed ultrasound image.
Recently, certain automated IMT measurement techniques have become available which improve the accuracy and precision of such measurements. However, even though absolute IMT measurements are improved by automated techniques, measurement of changes in arterial IMT and diameter over time, which indicates progression or regression of atherosclerosis, must also be accurate, and repeatable in both time and space. Carotid images, acquired in different examinations, must be precisely replicated since very small changes in the ultrasound view of the artery can cause large changes in the IMT or diameter measurements.
While standardized positioning procedures assist in minimizing changes, a patient's position on the examination table can rarely be reproduced exactly in different examinations. Thus, identical images cannot be obtained under these conditions. Attempts to superimpose images from different examinations using color coding or image subtraction have not been successful for both technical and procedural reasons since small differences in image acquisition, which are always present, as discussed above, are exaggerated in the superimposed color coded or subtracted images, making interpretation difficult at best. These image differences are driven by the limited reproducibility image acquisition techniques currently available.
The need for a standardized methodology by which carotid artery images are acquired and IMT and arterial dimensions are measured in an accurate and reproducible form will become apparent when it is recognized that ultrasonography has distinct advantages over any of the other techniques currently available for evaluating carotid arterial vascular structures such as the intima-media thickness and diameter, and physiologic structures such as arterial wall stiffness as cumulative measures of generalized atherosclerosis. In particular, high resolution B-mode ultrasonography is readily available to practitioners. It is inexpensive, easy to perform, poses no risk, and can be repeated as frequently as desired. Most importantly, it can be used in healthy, asymptomatic individuals to determine the extent and progression of atherosclerosis. Accurate determination of carotid arterial anatomy (IMT and diameter measurements) and physiology (stiffness and compliance) is possible, with the entire process of carotid artery image acquisition and measurement taking approximately 30 minutes.
Utilizing this technique, measurement of the rate of atherosclerosis progression can be envisioned as part of a yearly physical examination. Although readily employed as the most common measure of atherosclerosis progression in clinical trials and human studies, further standardization of this methodology for application in screening, prevention and treatment of atherosclerosis and cardiovascular and cerebrovascular disease is still required.
This needs to be accomplished at the earliest time possible, such that practitioners can more accurately and cost-effectively screen individuals at risk for a cardiovascular or cerebrovascular event and to design therapies on an individual basis in the prevention and treatment of atherosclerotic disease.